Greetings all,
Nigel already posted this on the ALNY board, but I thought it would be interesting to discuss on this board as well. By systemic delivery, I assume that they mean that the compound was introduced into the bloodstream generally (as opposed to the AMD trials where the siRNA is applied directly to the target cells).
Does anyone have a take on their liposomes delivery mechanism that got the siRNA into the liver? I know that has been talked about for some time, but would that delivery mechanism be allowed in humans? Thanks in advance.
Cheers,
Thomas
March 26, 2006 12:00 PM US Eastern Timezone
First Demonstration of Therapeutic Gene Silencing in Primates with Systemic RNAi Published in Nature by Alnylam Scientists; Systemic RNAi Shown to have Durable Effect and Feasible Dosage for Future Human Clinical Studies
CAMBRIDGE, Mass.--(BUSINESS WIRE)--March 26, 2006--
Company Holding Conference Call at 8:30 a.m. Monday, March 27, 2006 to Discuss Results
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today the first published demonstration in primates that a systemically delivered RNAi therapeutic can potently silence an endogenous disease-causing gene in a clinically relevant manner. Alnylam and its collaborators at Protiva Biotherapeutics, Inc., demonstrated silencing in primates of the gene for apolipoprotein B (apoB), a protein involved in cholesterol metabolism, with clinically significant efficacy as demonstrated by reductions in levels of cholesterol and low-density lipoproteins (LDL). This peer-reviewed research, published in the world-leading scientific journal Nature, represents a major advance because it suggests that an RNAi therapeutic can be effective when delivered systemically using a dosage appropriate for application in future human clinical studies.
In the published research, Alnylam scientists and collaborators demonstrated potent silencing in primates of the gene for apoB, a disease-causing protein which to date has not been amenable to targeting with traditional small molecule, protein, or antibody therapies. The achievement of this result by systemic administration through the bloodstream demonstrates the broad potential of RNAi therapeutics to target disease-causing genes, and significantly expands the previously demonstrated opportunity for RNAi therapeutics to treat human disease by direct administration to sites of disease, such as with respiratory or ocular delivery.
"We believe that these findings both advance the field of RNAi and expand the opportunity for RNAi therapeutics, as they represent a launching pad to extend beyond our current clinical efforts with direct RNAi therapeutics and address the broader potential of this promising technology with systemic RNAi. These data give us confidence that with further optimization of our systemic RNAi platform we can move a systemic RNAi therapeutic candidate into human clinical trials as early as the next 18-24 months," said John Maraganore, Ph.D., President and Chief Executive Officer of Alnylam Pharmaceuticals. "Publication of these robust and well-controlled results in a prestigious journal such as Nature is also further demonstration of Alnylam's leadership position in the field of RNAi, our commitment to scientific excellence and to applying this expertise for development of innovative medicines."
In the study published in Nature, Alnylam scientists and collaborators showed that systemic delivery in non-human primates of a chemically optimized small interfering RNA, or siRNA, can result in silencing of the apoB messenger RNA (mRNA), leading to significant reductions in blood levels of the apoB protein. These effects were proven to occur through an RNAi-mediated mechanism, and resulted in immediate, potent, and durable therapeutic efficacy. The siRNAs were formulated with liposomes that enable delivery to liver cells. The observed therapeutic effects included significant reductions in serum levels of cholesterol and LDL, which together represent the so-called "bad cholesterol" associated with development of atherosclerosis and coronary artery disease. Following administration of a single intravenous bolus dose at low dosages from 1.0-2.5 mg/kg, these reductions were observed as early as 24 hours after treatment and lasted for at least 11 days. A single siRNA injection resulted in dose-dependent silencing of apoB mRNA expression, with maximal silencing of over 90%. The silencing of apoB was proven to occur through an RNAi-mediated mechanism of action. In addition, plasma apoB levels were reduced by more than 75%, cholesterol levels by more than 60%, and LDL levels by more than 80%. In the study of 18 animals, the treatment was well tolerated with only transient liver enzyme elevation observed at the highest dose. We believe the rapid and durable silencing of apoB with RNAi is of clinical relevance, as it may represent a novel strategy for reducing LDL-cholesterol in several clinical settings.
Conference Call Information
On Monday March 27, 2006 at 8:.30 a.m. ET, Alnylam will hold a conference call to discuss the systemic delivery data published in Nature. The call may be accessed by dialing 800-435-1398 (domestic) or 617-614-4078 (international) five minutes prior to the start time, and providing the passcode 96061327. A replay of the call will be available from 11:00 a.m. ET on March 27, 2006 until April 3, 2006. To access the replay, please dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the passcode 76867418. A live audio webcast of the call will also be available on the "Investors" section of the Company's website, www.alnylam.com. An archived webcast will be available on the Alnylam website approximately two hours after the event, and will be archived for 14 days thereafter.
About RNA Interference (RNAi)
RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. RNAi is induced by small, double-stranded RNA molecules. RNAi is activated by chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing. Alnylam's initial drug development programs are focused on Direct RNAi(TM) therapeutics which are siRNAs administered directly to diseased parts of the body. In parallel, the company is developing Systemic RNAi(TM) therapeutics that travel through the bloodstream to reach diseased parts of the body.
About Alnylam
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is building a pipeline of RNAi therapeutics; its lead program is in Phase I human clinical trials for the treatment of respiratory syncytial virus (RSV) infection, which is the leading cause of hospitalization in infants in the U.S. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Merck, Medtronic, and Novartis. The company, founded in 2002, maintains global headquarters in Cambridge, Massachusetts, and has an additional operating unit in Kulmbach, Germany. Alnylam is honored to be the 'emerging/mid-cap' company recipient of the 2006 James D. Watson Helix Award, the biotechnology industry's award for outstanding achievement. For more information, please visit www.alnylam.com. |
